Method and Apparatus for Detection of Heartbeat Characteristics

ABSTRACT

Aspects of the present disclosure are directed to detecting Atrial Fibrillation (AF). As may be implemented in accordance with one or more embodiments, a time series of inter-beat intervals is computed from a recording of activity of a beating heart. The time series is decomposed into subcomponents, and an envelope of at least one of the subcomponents is computed. The presence of atrial fibrillation (AF) is detected based upon characteristics of the envelope that are indicative of AF.

FIELD OF INVENTION

Various aspects of the present invention relate to the processing ofphysiological signals, such as electrocardiogram (ECG) and other signalsindicative of the activity of a beating heart, and more particularaspects relate to detection of the presence of heartbeatcharacteristics.

BACKGROUND

Analysis of the character of the variability of heart beats can providevaluable insights that can be useful for diagnosis and monitoring ofpathological conditions such as atrial fibrillation (AF) or the presenceof other heartbeat characteristics such as ectopic beats. AF is acardiac disorder that occurs when the heart's upper chambers (the atria)quiver instead of beating effectively. With AF, blood may not be pumpedcompletely out of the atria, allowing blood to pool in the atria andeventually form a clot. If a clot migrates from the left atria it maytravel through the arterial system and lodge in the brain, resulting instroke. A high proportion of AF is asymptomatic and therefore one cannotrely on the patient to report its presence or absence. Assessing thepresence of AF is therefore important to establish a diagnosis, chooseappropriate therapy and monitor the patient following administration ofa therapeutic regimen to determine its effectiveness.

In a normal heart, electrical activity of the atria is quite regular.When the atria contracts, an ECG recorded from electrodes located on thechest will typically show a small deflection corresponding to electricalactivity in the atria (i.e. P-wave). When atrial electrical activityreaches the “atrioventricular” (AV) node, it is delayed to allow theatria to finish contracting and expelling blood into the ventricles.Following the delay in the AV node, the electrical activity travels intothe ventricles, causing them to contract and pump blood throughout thebody.

When AF is present, the AV node is bombarded with a highly variablelevel of electrical activity from the atria at a rate much faster thanits conduction delay can accommodate. As a result, much of theelectrical atrial activity from the atria is blocked. Due to this andthe stochastic nature of the atrial electrical activity, the AV nodestimulates the ventricles in an irregular pattern. AF can thereforeusually be detected by evaluating ventricular activity. When physiciansexamine ECG recordings for the presence of AF, they often describe whatthey are looking for in the ventricular rhythm as the degree ofirregularity in the irregularity. If the irregularity is regular, suchas in bigeminy or trigeminy, AF is not present. Likewise if the patienthas a strong sinus arrhythmia, as is often the case when a patient is ingood physical condition, the rhythm is irregular but is regularlyirregular. The irregularity has a regular pattern that correlates withrespiration. When AF occurs, the irregularity is highly stochastic.

AF is often transient and therefore requires that the patient bemonitored for days or weeks in order to obtain an accurate assessment ofthe presence of AF and the degree to which it is present (i.e. AFburden). This long-term monitoring often is performed with a smallbattery-powered wearable device that continuously evaluates the ECG anddetects the occurrence of AF and other cardiac arrhythmias. Since thedevice is battery powered, computational efficiency of the detectionalgorithm is important.

While approaches to AF detection have been implemented, theirimplementation has been challenging. For example, detection of AF basedupon the irregularity of ventricular rhythm can result in false positivedetections when, for example, the patient is experiencing bigeminy,trigeminy or strong sinus arrhythmia. In addition, many approaches arecomputationally burdensome, which can require large power consumption(e.g., resulting in the need for a large battery and hence large devicesize and weight), and suffer from short battery life.

SUMMARY

Various aspects of the present invention are directed to devices,computer implemented methods and systems for detecting the presence ofAF, in a manner that addresses challenges and limitations includingthose discussed above. Certain embodiments provide an indication of AFbased on the presence of ectopic beats, which can mitigate the detectionof false positive AF event detections. Accurate AF detection can beprovided by considering whether P-waves are present. In connection withvarious embodiments, it has been discovered that approaches ascharacterized herein can mitigate computational burden and lower powerconsumption.

In accordance with various example embodiments, QRS complexes aredetected in an ECG and a sequence of inter-beat intervals is computed.The sequence of inter-beat intervals is cleaned by identifying QRScomplexes to be excluded, reducing or eliminating inter-beat intervalsthat relied on excluded QRS complexes, and interpolating across the gapscreated by the excluded QRS complexes.

In one aspect, QRS complexes to be excluded are those that are detectedin error, were excessively noisy and hence of suspect accuracy, or werepart of a ventricular arrhythmia. The cleaned inter-beat intervalsequence is decomposed into subcomponents. As may be implemented withone or more embodiments, the interbeat interval sequence is resampled tocreate equispaced series prior to decomposition. In another embodimentthe decomposition is performed on interbeat interval sequence that isnot resampled. In one example embodiment, an envelope V(t) is computedusing one or more selected subcomponents. In one embodiment, onesubcomponent is selected and V(t) is computed as the absolute value orthe square root of the square of the selected subcomponent. In oneembodiment, the selected subcomponent is the subcomponent thatcorresponds to the highest frequency represented by the decomposition.In another embodiment, the envelope V(t) is computed using asubcomponent with a corresponding frequency in the range of 0.5 to 3 Hzfor adult human beings and 0.2 to 1 times the highest heart rate forother species. In another embodiment, an envelope V(t) is computed bycomputing the square root of the sum of the squares of two or moreselected subcomponents at each time point. In one embodiment theenvelope V(t) is computed by applying a low pass filter to thepoint-wise square of the selected subcomponents prior to computing thesquare root.

In an alternate embodiment a time-frequency spectrum is computed using,for example, continuous wavelet decomposition or short-term Fouriertransform. The resulting spectrum is divided into frequency bands, andenvelope V(t) is computed. V(t) in this embodiment represents the powerin one or more frequency bands as a function of time.

According to one aspect of the present invention, V(t) is compared to athreshold Vth. When V(t) exceeds the threshold Vth for more than apredetermined time T1 (e.g., a time exhibiting power greater than Vth inone or more frequency bands), a metric of the entropy SE(t) of one ormore subcomponents SUB(t) or their point-wise products is computed fromthe time when V(t) first crossed threshold Vth. If SE(t) is greater thana threshold SEth (an entropy threshold), the presence of AF isindicated. Such a threshold may, for example, pertain to a signal havingan irregularly irregular sequence of interbeat intervals.

Once the presence of AF is established, V(t) is evaluated to determineif the AF event has terminated. In one embodiment, V(t) is evaluatedrelative to a threshold Vthl to determine if the AF event hasterminated. If V(t) falls below threshold Vthl for a time >T2, then theabsence of AF is indicated. T1 and T2 are selected based upon clinicallysignificant intervals for which it is important to detect the presenceor absence of AF. In one embodiment T1 and T2 are at least 30 sec.

The above summary is not intended to describe each embodiment or everyimplementation of the present disclosure. The figures and detaileddescription that follow more particularly exemplify various embodiments.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention may be more completely understood in consideration of thefollowing detailed description of various embodiments of the inventionin connection with the accompanying drawings, in which:

FIG. 1 illustrates an apparatus for sensing, measuring and processing anECG signal for detecting the presence of AF;

FIG. 2 shows a flowchart describing signal flow for detecting thepresence and absence of AF;

FIG. 3 shows a plot of various signals computed before, during, andafter the detection of the presence of AF;

FIG. 4 shows a plot of various signals computed during and afterdetection of the presence of AF;

FIG. 5 shows an example embodiment for determining Vth and Vthl; and

FIG. 6 shows an example embodiment for determining signal entropythreshold SEth.

While the invention is amenable to various modifications and alternativeforms, specifics thereof have been shown by way of example in thedrawings and will be described in detail. It should be understood,however, that the intention is not to limit the disclosure to theparticular embodiments described. On the contrary, the intention is tocover all modifications, equivalents, and alternatives falling withinthe scope of the disclosure including aspects defined in the claims.

DETAILED DESCRIPTION

Various example embodiments of the present disclosure relate to methods,circuits, computer implemented software, devices and systems that usephysiological signals for detecting the presence or absence of AF. Whilethe present disclosure is not necessarily limited in this regard,various aspects of the disclosure may be appreciated through adiscussion of examples using this context.

As discussed hereinabove, various circuits, devices and systems thatprocess physiological signals (e.g., ambulatory ECG recordings) can bechallenging to implement for accurately detecting the presence andabsence of AF, and may not be efficient in use of power. Accuratedetection of AF presents a significant challenge to the implementationof such circuits, computer implemented software, devices and systems forcarrying out signal evaluation. Accordingly, various aspects of thepresent invention are directed to addressing these challenges.

In accordance with another example embodiment, a computer implementedmethod involves detecting the presence of AF in a recording of activityof a beating heart. A time series of inter-beat intervals is computedfrom the recording, and the time series is decomposed intosubcomponents. An envelope of at least one of the subcomponents iscomputed, and the presence of AF is detected based upon characteristicsof the envelope that are indicative of AF (e.g., based upon a comparisonof the envelope to a first threshold indicative of AF).

In some embodiments, computing a time series of inter-beat intervalsincludes detecting a plethora of heart beats, identifying invalid beatsfrom the detected beats, and computing a raw sequence of inter-beatintervals from consecutive ones of the detected beats. A cleanedsequence of inter-beat intervals is created/identified by excludingintervals computed using ones of the beats identified as being invalid.The cleaned sequence of inter-beat intervals is then resampled to createan equispaced time series of inter-beat intervals. In someimplementations, invalid beats are identified as beats characterized asone or more of ventricular arrhythmias, being detected in error, andexcessively noisy (e.g., beyond a noise threshold determined forparticular applications/desirable output).

Detecting the presence of AF can be carried out in a variety of manners.In some embodiments, detecting the presence of AF includes detecting thepresence of AF based upon an envelope exceeding a first threshold forpredetermined amount of time, as discussed above. In another embodiment,AF is detected based upon such an envelope exceeding the first thresholdfor a predetermined portion of a predetermined amount of time, and acomputed metric of entropy exceeding an entropy threshold. Certainembodiments involve computing the metric of entropy, such as for one ormore of the time series of inter-beat intervals, a subcomponent, and aproduct of subcomponents. In some embodiments, the metric of entropy iscomputed using one of sample entropy and approximate entropy. In anotherembodiment, AF is detected based upon an envelope falling below a secondthreshold for a predetermined portion of a predetermined time.

A variety of recordings may be processed in accordance with embodimentsdescribed herein. Such recordings may include, for example, anelectrocardiogram, a ballistocardiogram, heart sounds, blood pressure,blood flow in an artery, and a photoplethysmography signal of a bodytissue. In addition, decomposing the time series into subcomponents iscarried out in a variety of manners to suit particular embodiments, suchas by applying one of a discrete cosine transform, a stationary wavelettransform, a discrete wavelet transform, a filter bank, asynchrosqueezed wavelet transform, a Gabor transform, a short-termFourier transform, a continuous wavelet transform and a wavelet packettransform. In some embodiments, one or more of the subcomponents areidentified as a subcomponent having a frequency corresponding to ahighest frequency of the subcomponents.

In one embodiment the presence of AF is detected. Referring to FIG. 1,an ECG signal is captured via sensing electrode (or electrodes) 101, isamplified with amplifier 102, digitized with ADC 103, and the digitizedsignal is processed using a computerized algorithm implemented incomputing device 104. It should be recognized that signals other thanECG can be captured by sensing electrode 101 for detection of AF. Thesesignals include arterial blood pressure, a photoplethysmography signalobtained from the tissue, an acoustical signal sensed from the thorax,and a ballistocardiogram.

Referring to FIG. 2, a digitized ECG recording 200 is input in 201 andis processed using a computerized algorithm to identify the locations ofQRS complexes and a sequence of raw inter-beat intervals is computed asthe time between adjacent QRS complexes. In one embodiment, QRScomplexes are identified using an approach as described in U.S. Pat. No.8,632,465 and PCT publication PCT/US2013/024770. In another embodiment,QRS complexes are identified using a Pan-Tomkins approach as describedin Pan J., Tompkins W. A Real-Time QRS Detection Algorithm. IEEETransactions on Biomedical Engineering, vol. BME-32, no. 3, March 1985,which is fully incorporated herein by reference. In another embodiment,QRS complexes are identified using a Hilbert transform as described inU.S. Pat. No. 7,729,753.

In some embodiments, as shown in step 202, it is useful to create acleaned and equispaced sequence of inter-beat intervals. Cleaning can beaccomplished by identifying QRS complexes that were falsely triggered bynoise in the ECG recording or are associated with ventriculararrhythmias, ignoring associated inter-beat intervals, and interpolatingover the gaps created by ignoring these intervals. Ventriculararrhythmias can be identified using techniques as described hereinand/or well known in the art. Ventricular arrhythmias to be excluded mayinclude ectopic beats, ventricular tachycardia, pause and bradycardia.In some embodiments, detection of QRS complexes that are falselytriggered by noise is accomplished by measuring noise level in the ECGsignal and computing a confidence in the QRS detection based upon thelevel of noise. One technique for computing this confidence signal isdescribed in U.S. Pat. Nos. 8,632,465 and 8,433,395. Certain embodimentsemploy other techniques for noise measurement such as measurement ofzero crossings in the isoelectric line between T-wave offset and P-waveonset can also be used, for example, U.S. Pat. No. 7,515,955. In someembodiments, the cleaned sequence of RR intervals is fit with a cubicspline function and then resampled to create a cleaned and equispacedtime series of RR intervals. In another embodiment, the cleaned sequenceof RR intervals is linearly interpolated to create an equispaced seriesof RR intervals.

The time series resulting from step 202 is then decomposed intosubcomponents SUBi(t) in 203 using one of several transforms. In someembodiments the decomposition can be accomplished using one of adiscrete cosine transform, a stationary wavelet transform, a discretewavelet transform, a filter bank, a synchrosqueezed wavelet transform, aGabor transform, a short-term Fourier transform, continuous wavelettransform, or wavelet packet transform.

An envelope V(t) of a subcomponent SUBn(t) is computed in 204. In oneembodiment, envelope V(t) is computed using the subcomponentcorresponding to the highest frequency, SUBn(t). In some embodiments,the envelope is computed as the absolute value of SUBn(t), ABS(SUBn(t)).In other embodiments, ABS(SUBn(t)) is smoothed by applying a low-passfilter. In other embodiments V(t) is computed as the square root of thesquare of the subcomponent SUBn(t). In yet another embodiment, envelopeV(t) is computed using multiple subcomponents, each corresponding to adifferent frequency. In one embodiment, multiple subcomponents arecombined using various weighting factors applied to the absolute valuesof each subcomponent used to compute V(t).

In another embodiment, the envelope V(t) is computed using asubcomponent with a corresponding frequency in the range of 0.5 to 3 Hzfor adult human beings and 0.2 to 1 times the frequency corresponding tothe highest heart rate for other species. If V(t) exceeds apredetermined threshold for a time >T1, there is a preliminaryindication that AF may be present. Time interval T1 can be determined bythe shortest duration AF event that is desired to be detected. Forexample, if it is desired to detect AF events of 30 seconds and longer,T1 may be 30 seconds. In another embodiment, an envelope is computed asthe square root of the sum of the squares of two or more selectedsubcomponents at each time point. In one embodiment the envelope V(t) iscomputed by applying a low pass filter to the point-wise square of theselected subcomponents prior to computing the square root.

In another embodiment a time-frequency spectrum is computed using, forexample, a continuous wavelet decomposition or short-term Fouriertransform. The resulting spectrum is divided into frequency bands, andan envelope V(t) is computed on the selected frequency bands. Theenvelope V(t) in this embodiment, represents the power in a band offrequencies as a function of time.

Envelope V(t) is compared to a threshold Vth in 205. If V(t) exceeds Vthfor a predetermined time interval T1, a metric of signal regularity orcomplexity is computed. In another embodiment, V(t) must exceed Vth formore than a predefined portion of T1. In one embodiment, V(t) mustexceed Vth for at least 90% of T1. In another embodiment, V(t) mustexceed Vth for at least 60% of T1. In one embodiment, entropy SE(t) iscomputed as a metric of complexity. In some embodiments, SE(t) iscomputed using sample entropy as in Richman J S, Randall M J,“Physiological time-series analysis using approximate entropy and sampleentropy,” Am J Physiol Heart Circ Physiol 278:H2039-H2049 (2000), whichis fully incorporated herein by reference. In another embodiment SE(t)is computed using approximate entropy, such as in Pincus S M,“Approximate entropy as a measure of system complexity,” Proc Natl AcadSci USA 88:2297-2301 (1991), which is fully incorporated herein byreference. In other embodiments one or more of detrended fluctuationanalysis (DFA), correlation dimension, largest Lyapunov exponent,fractal dimension, Hurst exponent, and recurrence plots are used asmetrics of regularity or complexity. DFA quantifies the extent of shortand long-range correlations in a time series, via a metric called ascaling exponent. In one embodiment, the fluctuations of a detrendedintegrated time RR time series are calculated as root mean square valuesF(n) of individual subcomponents SUBn(t)s. The scaling exponent is thenapproximated as a slope α of the linear fit in the log-log plot: logF(n)=α log n. When scaling exponent a at around 0.5, the time seriesdynamic is similar to white noise, which is characteristic of RR timeseries in AF.

In one embodiment, the energy of higher frequency beat-to-beatfluctuations in RR interval is computed. In some embodiments prematurebeats are identified (premature beats of either ventricular or atrialorigin) and excluded prior to computing the energy of higher frequencybeat-to-beat fluctuations. This computed measure of energy is indicativeof the higher frequency changes in RR interval that correspond to thosetypical of AF. Lower frequency changes in RR interval that are notindicative of the presence of AF (e.g., those corresponding torespiratory sinus arrhythmia and changes in physical activity) are notincluded in this energy measure. An envelope of the higher frequencyenergy is computed. When the envelope exceeds a threshold for apredetermined time, the series of RR intervals is determined to besufficiently irregular to indicate that AF might be present. Once it isestablished that AF may be present, a metric of entropy (i.e., chaos) iscomputed for the series of RR intervals to confirm the presence of AF.In some embodiments it is advantageous to compute entropy only after afirst order irregularity is found because entropy algorithms aregenerally computationally demanding.

In one embodiment approximate entropy is computed as a measure of thedegree of chaos in the inter-beat time series. Approximate entropy (APE)quantifies the probability that a ‘similar’ pattern will not be followedby additional ‘similar’ patterns throughout the series. The algorithmfor computing APE depends upon two parameters: length of the chosenpattern (m) and threshold for similarity between patterns (r). Thealgorithm for computing APE involves computing conditional probabilitythat any two sequences of length m that match within tolerance of r willalso match at the m+1 point.

In another embodiment sample entropy is computed as a measure of thedegree of chaos in the inter-beat time series. Similar to approximateentropy the algorithm involves computing conditional probability ofpattern matching. In some embodiments, relative to sample entropy,approximate entropy compensates for bias introduced by matching atemplate to itself and the sensitivity of the conditional probability tothe time series length.

Entropy SE(t) is computed in 206 for a subcomponent SUBn(t) startingwhen V(t) first exceeds threshold Vth. In an alternate embodiment, SE(t)is computed from the RR time series. In yet another embodiment, SE(t) iscomputed from a product or a linear combination of the subcomponents. Inone embodiment, SE(t) is computed for consecutive one-minute segments.In other embodiments, entropy is computed for overlapping segments orsegments that are shorter or longer.

In yet another embodiment where V(t) is computed using subcomponentscorresponding to a band of frequencies in a time-frequency spectrum,SE(t) is computed using one or more subcomponents corresponding to aband of frequencies. In another embodiment SE(t) is computed using aproduct or a linear combination of the subcomponents corresponding tothe selected band of frequencies. If SE(t) exceeds a predeterminedthreshold SEth in 207, the presence of AF is detected in 208.

In one embodiment, the threshold Vth is determined empirically basedupon the characteristics of RR dynamics of the species. The secondthreshold Vthl evaluated in step 209, (i.e. the lower threshold thattogether with Vth provides hysteresis, or Schmitt trigger, operation fordetection of the presence and absence of AF) can be likewise determinedempirically. In one embodiment, Vth and Vthl are determined by computingenvelope V(t) for a representative ECG data set consisting of normalsinus rhythm and AF events. In one embodiment, amplitude of V(t) isplotted vs. rhythm classification (i.e. normal sinus rhythm and AF),resulting in two clusters as shown in FIG. 5. Thresholds Vth and Vthlare selected as values that separate the amplitudes of V(t) for thesetwo classifications to a desired statistical confidence level. In oneembodiment, Vth is chosen as the 10^(th) percentile of the envelopeamplitude for the AF cluster and Vthl is chosen as the 95^(th)percentile of the envelope amplitude for the normal sinus rhythmcluster. Percentiles used for determining Vth and Vthl can varydepending upon the desired tradeoff between sensitivity and specificityof AF detection performance.

FIG. 5 shows an example embodiment for how Vth and Vthl are determined.Cluster 501 consists of values of V(t) for normal sinus rhythm. Cluster502 includes values of V(t) for when AF is present. In this exampleembodiment, threshold Vth 503 is chosen as the 10^(th) percentile ofvalues of V(t) for AF events and Vthl 504 is chosen as the 95^(th)percentile of V(t) for ECG recordings classified as normal sinus rhythm.

In one embodiment, a metric of entropy SE(t) is used to discriminatebetween AF and rhythms that demonstrate a high degree of irregularity inRR interval, but are regular in the nature of the irregularity (i.e.bigeminy, trigeminy and respiratory sinus arrhythmia). SE(t) is comparedto a threshold SEth in 207 to discriminate between AF and rhythms thatare characteristically regular in the nature of their irregularity. Insome embodiments, threshold SEth in 207 in FIG. 2 is determinedempirically in a manner similar to how Vth and Vthl are determined. Inone embodiment, SE(t) is plotted vs. rhythm classification resulting intwo clusters: one for AF and a second corresponding to bigeminy,trigeminy and high amplitude respiratory sinus arrhythmia. In oneembodiment SEth is chosen as the 95^(th) percentile of the clustercomprised of rhythms having a characteristic of regular irregularitysuch as bigeminy, trigeminy and respiratory sinus arrhythmia. Thepercentile used for determining SEth can vary depending upon the desiredtradeoff between sensitivity and specificity of AF detectionperformance. In some embodiments, it may be useful to implement a secondthreshold such that hysteresis (i.e. Schmitt trigger functionalitysimilar to an embodiment of how V(t) evaluation vs. Vth and Vthl) can beimplemented to improve discrimination of AF from bigeminy, trigeminy andhigh amplitude respiratory sinus arrhythmia.

FIG. 6 shows an example embodiment demonstrating how SEth is determined.Cluster 601 consists of values of SE(t) for ECG strips where AF ispresent. Cluster 602 consists of values of SE(t) for when bigeminy,trigeminy or high amplitude respiratory sinus arrhythmia is present. Inthis example embodiment, threshold SEth 603 is chosen as about the95^(th) percentile of SE(t) for ECG recordings classified as bigeminy,trigeminy or high amplitude respiratory sinus arrhythmia.

Once the presence of AF has been detected, and referring again to FIG.2, envelope V(t) is evaluated to determine if AF is absent by comparingV(t) to a threshold Vthl in 209, where Vthl<Vth. In one embodiment, thealgorithm will continue to indicate that AF is present until V(t) fallsbelow Vthl for a predetermined time T2. In yet another embodiment, AF isdetected as being absent when V(t) falls below Vthl for at least 60% oftime T2. Once it is determined that AF is absent at 210, the algorithmwill then begin to look for the onset of AF by evaluating V(t) in 205.The process ends if the recording is complete at block 211, andcontinues at block 205 if not.

An example recording is shown in FIG. 3 for illustrative purposes.Traces 303, 304 and 305 are the subcomponents corresponding to thehighest three frequencies following decomposition. Envelope 301 iscomputed using subcomponent 304, the second highest frequencysubcomponent and corresponds to V(t) computed in 204 of FIG. 2.Threshold 309 corresponds to Vth in 205 of FIG. 2 and SE(t) 302 showsthe entropy metric over time as computed in 206 of FIG. 2. In thisexample, entropy is computed on one minute segments of subcomponent 304.The value of entropy metric SE(t) at about 13.5 minutes, for example, iscomputed based upon subcomponent 304 in the prior one minute segment.

FIG. 3 begins at about 8 minutes into the recording with the presence ofAF having already been detected. Envelope V(t) 301 remains abovethreshold Vthl 310 until about time 9.2 minutes. V(t) 301 falls belowVthl 310 and remains below threshold 310 for the requisite time T2 asexamined in 209 of FIG. 2. The absence of AF is indicated at verticaldashed marker 306 at the time point where V(t) 301 falls below Vthl 310.

The recording then progresses in time with V(t) 301 below Vth 309 untilabout time 11.1 minutes. V(t) 301 then crosses threshold Vth 309 andremains above for the requisite time. SE(t) 302 at 11.5 minutes, thevalue computed for the prior one minute segment, is above threshold SEth302 and therefore the presence of AF is indicated where V(t) 301 firstcrossed threshold Vth 309 indicated by marker 307. V(t) 301 remainsabove threshold Vthl 310 until about time 13.3 minutes. However, anepisode of bigeminy starts at about 12.8 minutes, causing entropy metric302 computed at time 13.5 minutes to fall below threshold SEth. Theabsence of AF is therefore indicated 30 seconds prior to where entropymetric 302 was computed (one-half the 60 second segment length used forcomputing entropy) per marker 308. Note that V(t) remains well aboveVthl until about time 13.3 minutes.

FIG. 4 provides an enlarged view of FIG. 3 from about 11.8 to 14.2minutes for illustrative purposes. Note that subcomponent 401transitions from chaotic to regular at about 12.8 minutes, the pointwhere the ECG transitions from AF to bigeminy. Entropy metric 404computed at time 13.5 minutes includes a portion of subcomponent 404which was chaotic for about the first 20 seconds and regular for thelast 40 seconds. Entropy metric 404 was evaluated vs. SEth (as in step207 of FIG. 2) at time 13.5 minutes and was found to be below thresholdSEth 403. The absence of AF was therefore indicated 30 seconds prior atmarker 402.

A challenge to the accurate determination of the presence of AF is theability to detect a type of ventricular arrhythmia referred to asectopic beats and exclude the corresponding inter-beat intervals. Insome patients ectopic beats occur frequently and in an irregularpattern. In order to avoid false positive detections of AF, it isnecessary to detect most of these ectopic beats and exclude them in step202 of FIG. 2 while creating a cleaned sequence of inter-beat intervals.In some embodiments, the incidence of ectopic beats is detected and/orreported, such as to provide diagnostic information for patientmanagement or to assess the effect of a drug or other therapy.

In some embodiments, detection of ectopic beats can be achieved bydecomposing the input ECG signal into subcomponents and computing theratio of the energy of one or more low-frequency subcomponents to theenergy of one or more high-frequency subcomponents. In one embodiment, awindow is formed around a detected ventricular depolarization (e.g., asdetected when a ventricle contracts, as may relate to the QRS complex orectopic beats). The depolarization may consist of a sinus complex or anectopic ventricular beat. Energy contained in two or more scales withinthe window is computed and compared to assess whether the beat containedin the window is a sinus complex or an ectopic beat. In one embodimentthe two or more scales consist of a low-frequency scale and a highfrequency scale. In some embodiments energy of a scale is computed asthe sum of squares of the amplitude of points within the window. Inother embodiments energy is computed as the sum of the absolute valuesof the amplitude. In some embodiments the energy contained in alow-frequency scale and a high-frequency scale is computed within thewindow and the ratio of the energy in the lower frequency scale and thehigher frequency scale is compared to a threshold. In some embodiments,if the energy in the lower-frequency scale is more than about 2.5 timesthe energy in the higher-frequency scale, the detected ventriculardepolarization is characterized as an ectopic beat (e.g., with energyconcentrated mainly in the lower-frequency scale). In anotherembodiment, a statistical evaluation of ratios for beats in the seriesis performed to find an appropriate threshold for the energy ratio.

In some embodiments, the accuracy of AF detection can be improved bydetecting the presence or absence of P-waves. In one embodiment,inter-beat intervals are evaluated, and if the evaluation indicates thepresence of AF in the recording, the portion of the recording where AFhas been detected is evaluated for the presence of P-waves. If P-wavesare consistently found in that portion of the recording AF is consideredabsent.

Various blocks, modules or other circuits may be implemented to carryout one or more of the operations and activities described herein and/orshown in the figures. In these contexts, a “block” (also sometimes“logic circuitry” or “module”) is a circuit that carries out one or moreof these or related operations/activities (e.g., computing a time seriesof beat-to-beat intervals, denoising into subcomponents, computing anenvelope and/or detecting the presence of AF). For example, in certainof the above-discussed embodiments, one or more modules are discretelogic circuits or programmable logic circuits configured and arrangedfor implementing these operations/activities, as in the circuit modulesshown in FIG. 1. In certain embodiments, such a programmable circuit isone or more computer circuits programmed to execute a set (or sets) ofinstructions (and/or configuration data). The instructions (and/orconfiguration data) can be in the form of firmware or software stored inand accessible from a memory (circuit). As an example, first and secondmodules include a combination of a CPU hardware-based circuit and a setof instructions in the form of firmware, where the first module includesa first CPU hardware circuit with one set of instructions and the secondmodule includes a second CPU hardware circuit with another set ofinstructions.

Certain embodiments are directed to a computer program product (e.g.,non-volatile memory device), which includes a machine orcomputer-readable medium having stored thereon instructions which may beexecuted by a computer (or other electronic device) to perform theseoperations/activities.

Based upon the above discussion and illustrations, those skilled in theart will readily recognize that various modifications and changes may bemade to the various embodiments without strictly following the exemplaryembodiments and applications illustrated and described herein. Forexample, different thresholds may be used to achieve results applicableto specific embodiments and applications. In addition, the variousembodiments described herein may be combined in certain embodiments, andvarious aspects of individual embodiments may be implemented as separateembodiments. Such modifications do not depart from the true spirit andscope of various aspects of the invention, including aspects set forthin the claims.

1. A method comprising: computing a time series of inter-beat intervalsfrom a recording of activity of a beating heart; decomposing the timeseries of inter-beat intervals into subcomponents; computing the energyof at least two of the subcomponents; and determining that atrialfibrillation is absent based upon relative energy of the at least twosubcomponents.